FORMULATION OPTIMIZATION OF FENUGREEK EXTRACT LOADED NANO-STRUCTURED LIPID-DRUG-CARRIER FOR EFFECTIVE ORAL DELIVERY
DOI:
https://doi.org/10.22159/ajpcr.2025v18i11.56511Keywords:
Trigonella foenum-graecum, Lipid nanoparticles, Bioavailability enhancement, Experimental design, Sustained release, Intestinal absorption.Abstract
Objectives: The present work focused on designing, optimizing, and evaluating solid lipid nanoparticles (SLNs) for the oral delivery of fenugreek extract (FE) to achieve enhanced systemic bioavailability, higher gastrointestinal absorption, and sustained release kinetics.
Methods: A Box-Behnken statistical design was implemented to optimize FE-SLNs formulation by systematically varying lipid (compritol 888 ATO), surfactant (polyvinyl alcohol), and homogenization speed as processing parameter. Critical quality attributes including mean particle size, polydispersity index (PDI), surface charge (zeta potential), encapsulation efficiency (%EE), and release behavior (% cumulative drug release [CDR]) were analyzed. The final formulation was further characterized by advanced analytical techniques (transmission electron microscopy, differential scanning calorimeter) and evaluated for ex vivo intestinal permeation.
Results: The optimized FE-SLNs demonstrated favorable characteristics, average diameter (460 nm), uniform distribution (PDI 0.233), surface charge (−14.1 mV), and %EE (47.56%). In vitro studies showed %CDR (79.66% over 12 h). Permeation assessments revealed significantly enhanced absorption compared to FE solution, with permeability coefficients increasing from 2.9×10−3 cm/h (FE solution) to 6.3×10−3 cm/h (developed formulation).
Conclusion: The developed FE-SLNs system exhibited optimal physicochemical properties and enhanced absorption potential, demonstrating its successful formulation. The sustained release profile following Higuchi kinetics suggested that these nanoparticles could serve as an effective platform for oral administration of natural bioactives.
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1. Dehariya P, Soni R, Paswan SK, Soni PK. Design of experiment based formulation optimization of chitosan-coated nano-liposomes of progesterone for effective oral delivery. J Appl Pharm Sci. 2023;13(06):256-70. doi: 10.7324/JAPS.2023.142351
2. Alqahtani MS, Kazi M, Alsenaidy MA, Ahmad MZ. Advances in oral drug delivery. Front Pharmacol. 2021;12:618411. doi: 10.3389/ fphar.2021.618411, PMID 33679401
3. Ahadian S, Finbloom JA, Mofidfar M, Diltemiz SE, Nasrollahi F, Davoodi E, et al. Micro and nanoscale technologies in oral drug delivery. Adv Drug Deliv Rev. 2020;157:37-62. doi: 10.1016/j. addr.2020.07.012, PMID 32707147
4. Homayun B, Lin X, Choi HJ. Challenges and recent progress in oral drug delivery systems for biopharmaceuticals. Pharmaceutics. 2019;11(3):129. doi: 10.3390/pharmaceutics11030129, PMID 30893852
5. Opanasopit P, Aumklad P, Kowapradit J, Ngawhiranpat T, Apirakaramwong A, Rojanarata T, et al. Effect of salt forms and molecular weight of chitosans on in vitro permeability enhancement in intestinal epithelial cells (Caco-2). Pharm Dev Technol. 2007;12(5):447- 55. doi: 10.1080/10837450701555901, PMID 17963144
6. Hua S. Advances in oral drug delivery for regional targeting in the gastrointestinal tract - influence of physiological, pathophysiological and pharmaceutical factors. Front Pharmacol. 2020;11:524. doi: 10.3389/fphar.2020.00524, PMID 32425781
7. Yadav UC, Baquer NZ. Pharmacological effects of Trigonella foenum-graecum L. in health and disease. Pharm Biol. 2014;52(2):243-54. doi: 10.3109/13880209.2013.826247, PMID 24102093
8. Sindhu RK, Goyal A, Algın Yapar EA, Cavalu S. Bioactive compounds and nanodelivery perspectives for treatment of cardiovascular diseases. Appl Sci. 2021;11(22):11031. doi: 10.3390/app112211031
9. Walia A, Gupta AK, Sharma V. Role of bioactive compounds in human health. Acta Sci Med Sci. 2019;3(9):25-33.
10. Gershenzon J, Dudareva N. The function of terpene natural products in the natural world. Nat Chem Biol. 2007;3(7):408-14. doi: 10.1038/ nchembio.2007.5, PMID 17576428
11. Dar RA, Shahnawaz M, Ahanger MA, Majid I. Exploring the diverse bioactive compounds from medicinal plants: A review. J Phytopharmacol. 2023;12(3):189-95. doi: 10.31254/phyto.2023.12307
12. Block E. The chemistry of garlic and onions. Sci Am. 1985;252(3):114-9. doi: 10.1038/scientificamerican0385-114, PMID 3975593
13. Calder PC. Polyunsaturated fatty acids and inflammation. Prostaglandins Leukot Essent Fatty Acids. 2006;75(3):197-202. doi: 10.1016/j. plefa.2006.05.012, PMID 16828270
14. Lv Y, Li W, Liao W, Jiang H, Liu Y, Cao J, et al. Nano-drug delivery systems based on natural products. Int J Nanomedicine. 2024;19:541-69. doi: 10.2147/IJN.S443692, PMID 38260243
15. Kumari S, Goyal A, Sönmez Gürer E, Algın Yapar E, Garg M, Sood M, et al. Bioactive loaded novel nano-formulations for targeted drug delivery and their therapeutic potential. Pharmaceutics. 2022;14(5):1091. doi: 10.3390/pharmaceutics14051091, PMID 35631677
16. Sarwar S, Hanif MA, Ayub MA, Boakye YD, Agyare C. Fenugreek. In: Medicinal Plants of South Asian. Netherlands: Elsevier; 2020. p. 257-71. doi: 10.1016/B978-0-08-102659-5.00020-3
17. Jhajhria A, Kumar K. Fenugreek with its medicinal applications. Int J Pharm Sci Rev Res. 2016;41(1):194-201.
18. Yao D, Zhang B, Zhu J, Zhang Q, Hu Y, Wang S, et al. Advances on application of fenugreek seeds as functional foods: Pharmacology, clinical application, products, patents and market. Crit Rev Food Sci Nutr. 2020;60(14):2342-52. doi: 10.1080/10408398.2019.1635567, PMID 31286789
19. Tewari A, Singh R, Brar JK. Pharmacological and therapeutic properties of fenugreek (Trigonella foenum-graecum) seed: A review. J Phytopharmacol. 2024;13(2):97-104. doi: 10.31254/phyto.2024.13203
20. Majumder J, Taratula O, Minko T. Nanocarrier-based systems for targeted and site specific therapeutic delivery. Adv Drug Deliv Rev. 2019;144:57-77. doi: 10.1016/j.addr.2019.07.010, PMID 31400350
21. Lin CH, Chen CH, Lin ZC, Fang JY. Recent advances in oral delivery of drugs and bioactive natural products using solid lipid nanoparticles as the carriers. J Food Drug Anal. 2017;25(2):219-34. doi: 10.1016/j. jfda.2017.02.001, PMID 28911663.
22. Pathak K, Raghuvanshi S. Oral bioavailability: Issues and solutions via nanoformulations. Clin Pharmacokinet. 2015;54(4):325-57. doi: 10.1007/s40262-015-0242-x, PMID 25666353
23. Reinholz J, Landfester K, Mailänder V. The challenges of oral drug delivery via nanocarriers. Drug Deliv. 2018;25(1):1694-705. doi: 10.1080/10717544.2018.1501119, PMID 30394120
24. Sadeghi S, Lee WK, Kong SN, Shetty A, Drum CL. Oral administration of protein nanoparticles: An emerging route to disease treatment. Pharmacol Res. 2020;158:104685. doi: 10.1016/j.phrs.2020.104685,
PMID 32097749
25. Paliwal R, Paliwal SR, Kenwat R, Kurmi BD, Sahu MK. Solid lipid nanoparticles: A review on recent perspectives and patents. Expert Opin Ther Pat. 2020;30(3):179-94. doi: 10.1080/13543776.2020.1720649, PMID 32003260
26. Kathe N, Henriksen B, Chauhan H. Physicochemical characterization techniques for solid lipid nanoparticles: Principles and limitations. Drug Dev Ind Pharm. 2014;40(12):1565-75. doi: 10.3109/03639045.2014.909840, PMID 24766553
27. Akbari J, Saeedi M, Ahmadi F, Hashemi SM, Babaei A, Yaddollahi S, et al. Solid lipid nanoparticles and nanostructured lipid carriers: A review of the methods of manufacture and routes of administration. Pharm Dev Technol. 2022;27(5):525-44. doi: 10.1080/10837450.2022.2084554, PMID 35635506
28. Mirchandani Y, Patravale VB, Brijesh S. Solid lipid nanoparticles for hydrophilic drugs. J Control Release. 2021;335:457-64. doi: 10.1016/j. jconrel.2021.05.032, PMID 34048841
29. Harde H, Das M, Jain S. Solid lipid nanoparticles: An oral bioavailability enhancer vehicle. Expert Opin Drug Deliv. 2011;8(11):1407-24. doi: 10.1517/17425247.2011.604311, PMID 21831007
30. Ganesan P, Narayanasamy D. Lipid nanoparticles: Different preparation techniques, characterization, hurdles, and strategies for the production of solid lipid nanoparticles and nanostructured lipid carriers for oral drug delivery. Sustain Chem Pharm. 2017;6:37-56. doi: 10.1016/j. scp.2017.07.002
31. Viegas C, Patrício AB, Prata JM, Nadhman A, Chintamaneni PK, Fonte P. Solid lipid nanoparticles vs. nanostructured lipid carriers: A comparative review. Pharmaceutics. 2023;15(6):1593. doi: 10.3390/ pharmaceutics15061593, PMID 37376042
32. Mishra V, Bansal KK, Verma A, Yadav N, Thakur S, Sudhakar K, et al. Solid lipid nanoparticles: Emerging colloidal Nano drug delivery systems. Pharmaceutics. 2018;10(4):191. doi: 10.3390/ pharmaceutics10040191, PMID 30340327
33. Salah E, Abouelfetouh MM, Pan Y, Chen D, Xie S. Solid lipid nanoparticles for enhanced oral absorption: A review. Colloids Surf B Biointerfaces. 2020;196:111305. doi: 10.1016/j.colsurfb.2020.111305, PMID 32795844
34. Mukherjee S, Ray S, Thakur RS. Solid lipid nanoparticles: A modern formulation approach in drug delivery system. Indian J Pharm Sci. 2009;71(4):349-58. doi: 10.4103/0250-474X.57282, PMID 20502539
35. Rahman Z, Zidan AS, Khan MA. Non-destructive methods of characterization of risperidone solid lipid nanoparticles. Eur J Pharm Biopharm. 2010;76(1):127-37. doi: 10.1016/j.ejpb.2010.05.003, PMID 20470882
36. Chandwani S, Saini TR, Soni R, Paswan SK, Soni PK. Box-Behnken design optimization of salicylic acid loaded liposomal gel formulation for treatment of foot corn. Int J Appl Pharm. 2023;15(3):220-33. doi: 10.22159/ijap.2023v15i3.47455
37. Prakash A, Soni PK, Paswan SK, Saini TR. Formulation and optimization of mucoadhesive buccal film for nicotine replacement therapy. Int J Appl Pharm. 2023;15(3):100-12. doi: 10.22159/ijap.2023v15i3.47412
38. Soni PK, Saini TR. Non-ionic surfactant vesicles (niosomes) based novel ophthalmic formulation of timolol maleate. J Drug Deliv Ther. 2017;7(7):59-61. doi: 10.22270/jddt.v7i7.1587
39. Soni PK, Saini TR. Purification of drug loaded liposomal formulations by a novel stirred cell ultrafiltration technique. Pharm Nanotechnol. 2021;9(5):347-60. doi: 10.2174/2211738509666211124145848, PMID 34819014
40. Soni PK, Saini TR. Development and evaluation of HP-β-CD complexation based novel ophthalmic gel formulation of nepafenac. Int J Pharm Sci Res. 2019;10(12):5707-14. doi: 10.13040/ IJPSR.0975-8232.10(12).5707-14
41. Pandita D, Kumar S, Poonia N, Lather V. Solid lipid nanoparticles enhance oral bioavailability of resveratrol, a natural polyphenol. Food Res Int. 2014;62:1165-74. doi: 10.1016/j.foodres.2014.05.059
42. Jain P, Soni R, Paswan SK, Soni PK. Ketoconazole laden microemulsion based gel formulation against skin fungal infection. Int J Appl Pharm. 2023;15(3):49-60. doi: 10.22159/ijap.2023v15i3.47456
43. Available from: https://www.himedialabs.com/in/la395-dialysis-membrane-110.html [Last accessed on 2025 Jan 08].
44. Paswan SK, Saini TR. Comparative evaluation of in vitro drug release methods employed for nanoparticle drug release studies. Diss Technol. 2021;28(4):30-8. doi: 10.14227/DT280421P30
45. Soni PK, Saini TR. Formulation design and optimization of cationic-charged liposomes of brimonidine tartrate for effective ocular drug delivery by design of experiment (DoE) approach. Drug Dev Ind Pharm. 2021;47(11):1847-66. doi: 10.1080/03639045.2022.2070198, PMID 35484943
46. Chaturvedi P, Soni PK, Paswan SK. Designing and development of gastroretentive mucoadhesive microspheres of cefixime trihydrate using spray dryer. Int J Appl Pharm. 2023;15(2):185-93. doi: 10.22159/ ijap.2023v15i2.45399
47. Paswan SK. Designing and characterization of polymeric microparticles containing agomelatine-loaded mesoporous silica nanoparticles for a controlled drug delivery system. Asian J Pharm. 2023;17(3):400-11. doi: 10.22377/ajp.v17i03.4982
48. Gamboa JM, Leong KW. In vitro and in vivo models for the study of oral delivery of nanoparticles. Adv Drug Deliv Rev. 2013;65(6):800-10. doi: 10.1016/j.addr.2013.01.003, PMID 23415952
49. Foudah AI, Ayman Salkini M, Alqarni MH, Alam A. Preparation and evaluation of antidiabetic activity of mangiferin-loaded solid lipid nanoparticles. Saudi J Biol Sci. 2024;31(4):103946. doi: 10.1016/j. sjbs.2024.103946, PMID 38384280
50. Jafari SM, Assadpoor E, He Y, Bhandari B. Re-coalescence of emulsion droplets during high-energy emulsification. Food Hydrocoll. 2008;22(7):1191-202. doi: 10.1016/j.foodhyd.2007.09.006
51. Anton N, Benoit JP, Saulnier P. Design and production of nanoparticles formulated from nano-emulsion templates-a review. J Control Release. 2008;128(3):185-99. doi: 10.1016/j.jconrel.2008.02.007, PMID 18374443
52. Müller RH, Mäder K, Gohla S. Solid lipid nanoparticles (SLN) for controlled drug delivery - a review of the state of the art. Eur J Pharm Biopharm. 2000;50(1):161-77. doi: 10.1016/s0939-6411(00)00087-4, PMID 10840199
53. Rao H, Ahmad S, Madni A, Rao I, Ghazwani M, Hani U, et al. Compritol-based alprazolam solid lipid nanoparticles for sustained release of alprazolam: Preparation by hot melt encapsulation. Molecules. 2022;27(24):8894. doi: 10.3390/molecules27248894, PMID 36558027
54. Hassan H, Bello RO, Adam SK, Alias E, Meor Mohd Affandi MM, Shamsuddin AF, et al. Acyclovir-loaded solid lipid nanoparticles: Optimization, characterization and evaluation of its pharmacokinetic profile. Nanomaterials (Basel). 2020;10(9):1785. doi: 10.3390/ nano10091785, PMID 32916823
55. Das S, Chaudhury A. Recent advances in lipid nanoparticle formulations with solid matrix for oral drug delivery. AAPS PharmSciTech. 2011;12(1):62-76. doi: 10.1208/s12249-010-9563-0, PMID 21174180
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Copyright (c) 2025 Aditi Agrawal, Prakash Kumar Soni, Reena Soni, Suresh Kumar Paswan
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